1. Field of the Invention
This invention relates to a process for producing 17-acetals of 3-alkoxyestra-2,5(10)-dien-17-ones. (The term acetal as used herein is synonymous with ketal.) More particularly, this invention relates to a commercially practical process for producing 17-acetals of 3-alkoxyestra-2,5(10)-dien-17-ones by Birch reduction of 17-acetals of 3-alkoxyestra-1,3,5(10)-trien-17-ones.
The 17-acetals of the 3-alkoxyestra-2,5-(10)-dien-17-ones are useful as intermediates in the preparation of steroidal hormones such as 19-norethisterone.
2. Description of the Prior Art
Japanese Patent Published 17,030/1960 discloses a process for producing 3-methoxyestra-2,5(10)-dien-17-one ethylene acetal, which comprises reacting 3-methoxyestra-1,3,5(10)-trien-17-one ethylene acetal with lithium or sodium, liquid ammonia and isopropanol in the presence of ethyl ether. This process has the disadvantage of using larger amounts of ethyl ether and liquid ammonia.
It is known that a 1,4-dihydrosteroid e.g., 3-methoxyestra-2,5(10)-dien-17-one diethyl acetal, is produced by reacting an aromatic steroid, e.g., 3-methoxyestra-1,3,5(10)-trien-17-one diethyl acetal with lithium or sodium, liquid ammonia and tert-butanol in the presence of tetrahydrofuran. (See Organic Reactions in Steroid Chemistry edited by John Fried and John A. Edwards, Van Nostrand Reinhold Company, in volume 1 at pages 25-27 and 49-50, and J. Org. Chem., 26 3237-3245 (1961)).
A disadvantage of this purpose is that the use of larger amounts of tert-butanol serving as a proton donor as well as a solvent results in lower reaction rates.
It is believed that impurities present in the starting materials such as 17-acetals of 3-alkoxyestra-1,3,5(10)-trien-17-ones and liquid ammonia, and solvents have a deleterious effect on the conversion of the 17-acetals of the 3-alkoxyestra-1,3,5(10-trien-17-ones to the 17-acetals of the 3-alkoxyestra-2,5(10)-dien-17-ones. This can be avoided by the purification of the starting materials and the solvents, which, however, is not economically attractive because of a decrease in the total yield of the 17-acetals of the 3-alkoxyestra-2,5(10)-dien-17-ones and a loss of the solvents.
It is therefore an object of this invention to provide a process that is capable of producing 17-acetals of 3-alkoxyestra-2,5(10)-dien-17-ones from 17-acetals of 3-alkoxyestra-1,3,5(10)-trien-17-ones in high yields and selectivities. It is another object to produce 17-acetals of 3-alkoxyestra-2,5(10)-dien-17-ones by a process which does not suffer from the disadvantages associated with processes employing larger volumes of a solvent, e.g., ethyl ether, tert-butanol, and liquid ammonia.
Still another object of this invention is to provide a commercially practical process for producing 17-acetals of 3-alkoxyestra-2,5(10-dien-17-ones which permits reliable and reproducible manufacturing operation. These and other objects are accomplished by the invention described herein.